tbuckley/cabot-search huggingface dataset:
Detection of molecular residual disease (MRD) for cancer management: Lessons from longitudinal profiling of NSCLC patients undergoing chemotherapy or targeted therapy.
Authors: Pei-Sung Hsu, Daniel Chen, Hui-Ping Chien, Chen Yeh, Peter Hong, Shu-Ti Lin, John-See Lee, Hung-Chih Lai
Journal: Journal of Clinical Oncology (2022)

e15020 Background: Identification of cancer patients who are at ongoing risk of relapse remains of high priority to direct effective adjuvant therapy. Plasma circulating cell-free DNA (cfDNA) analyses offer an unprecedented approach to identify patients with molecular residual disease (MRD) earlier than clinical or radiological evidence, detecting drug resistance, progression and relapse with relatively high sensitivity and specificity. Here we used longitudinal surveillance to profile cfDNA mutational landscape undergoing chemotherapy or EGFR-TKI. We demonstrated how cutting-edge NGS and digital qPCR technologies are defining new subgroups of patients with MRD for individually tailored treatment strategy. Methods: Plasma samples were collected from 8 subjects with lung adenocarcinoma, 5 patients were treated with EGFR-TKI and 3 cases by chemotherapy. Overall, 92 longitudinally collected specimens (duration of 31-143 weeks) were analyzed with a 520-gene ultra-deep NGS platform as well as a digital qPCR assay. Standard-of-care tests of CEA, CA19-9 biomarkers and CT radiography were also performed in parallel. Results: The number of somatic mutations detected ranging from 0 to 52 in a sample and correlated strongly with TMB (tumor mutational burden). The concordance of actionable EGFR mutations (L858R, T790M, Ex19Del) detected by NGS and digital qPCR assays was 100% (n = 49/49). NGS assay detected additional driver mutations in ∼20 non-EGFR genes. Majority of EGFR mutations showed directional decline in allelic fraction (AF) after treatment with EGFR-TKI. Patient progressed following EGFR-TKI were registered to undergo chemotherapy based on real-time mutational profiles and did show good responses and PFS. Longitudinal ultra-deep NGS analyses can help detect and stratify MRD, including non-druggable genetic information that could guide best clinical decision-making. Conclusions: Longitudinal ctDNA surveillance of patients treated with EGFR-TKI by a highly sensitive multi-gene NGS panel enables MRD monitoring and can potentially guide a selection of optimal adjuvant therapies earlier, and provide new surrogate endpoints for early registration of these therapies.
Grade and stage misclassification in unfavorable intermediate vs high-risk NCCC prostate cancer candidates for RT plus short vs long-term androgen ADT
Authors: G. Sorce, R.S. Flammia, B. Hoeh, F. Chierigo, L. Hohenhorst, E. Mazzone, A. Stabile, G. Gandaglia, Z. Tian, D. Tilki, C. Terrone, M. Gallucci, F.K.H. Chun, F. Saad, S.F. Shariat, A. Briganti, F. Montorsi, P.I. Karakiewicz
Journal: European Urology (2022)
Exploring Potential Modifiers of the Association Between Neurodevelopmental Disorders and Risk of Bullying Exposure
Authors: Evelina Käld, Linda Beckman, Valsamma Eapen, Ping-I Lin
Journal: JAMA Pediatrics (2022)

This survey study examines data from the National Survey of Children’s Health to determine which sociodemographic factors might modify the association between neurodevelopmental disorders and being bullied.
A randomized, non-comparative, phase II study of maintenance OSE2101 vaccine alone or in combination with nivolumab (nivo) or FOLFIRI after induction with FOLFIRINOX in patients (Pts) with advanced pancreatic ductal adenocarcinoma (aPDAC): First interim results of the TEDOPAM GERCOR D17-01 PRODIGE 63 STUDY.
Authors: Marc Hilmi, Emmanuel Mitry, Anthony Turpin, Olivier Bouché, Jean-Philippe Metges, François Ghiringhelli, Isabelle Trouilloud, Gaël Roth, Isabelle Baumgaertner, Christophe Borg, Hanifa Ammarguellat, Marielle Guillet, Yves Rinaldi, Thierry Lecomte, Christophe Louvet, Aurélien Lambert, Vincent Hautefeuille, Marie-Line Garcia-Larnicol, Julie Henriques, Cindy Neuzillet
Journal: Journal of Clinical Oncology (2022)

4148 Background: OSE2101 is a multiple neoepitope vaccine restricted to HLA-A2 positive Pts. This study aimed to assess the efficacy and safety of OSE2101 ± anti-PD1 nivo as maintenance therapy in Pts with aPDAC after FOLFIRINOX induction chemotherapy. Methods: TEDOPaM-PRODIGE 63 was initially a 3-arm, open-label, randomized, non-comparative phase II study. Pts with aPDAC, HLA-A2 positive (blood) and no progression after 8 cycles of (modified) FOLFIRINOX were randomized 1:1:1 to receive FOLFIRI (standard Arm A), OSE2101 (subcutaneous injection on D1 Q3W x 6 doses then Q8W until M12 then Q12W up to M24, experimental Arm B) or OSE2101 + nivo (360 mg IV on D1 Q3W x 6 then 480 mg Q4W up to M24, experimental Arm C). FOLFIRI was reintroduced at disease progression in Arms B and C. Primary endpoint was overall survival (OS) rate at 12 months (M12) (Fleming two-stage design, H0: 25%; H1: 50%, one-sided alpha: 2.5%, power: 90%). 156 Pts were planned. Results: Following the occurrence of 2 tumor flares in Arm C, an Independent Data Monitoring Committee (IDMC) recommended to continue FOLFIRI as backbone in experimental Arm B and stop Arm C. Interim analysis results refer to 29 randomized Pts: 9/10/10 in Arm A/B/C, respectively. Median age was 63 years, 52% were men, 55% had ECOG PS 0, and 83% were metastatic. Best response to induction FOLFIRINOX was partial response in 48% and stable disease in 52%. With a median follow-up of 23 months, M12-OS rate was 44%, 40%, and 30% in Arm A, B and C. Other efficacy results are summarized in Table below. No OSE2101-related toxicity of grade ≥ 3 (G≥3) were observed in Arm B; 1 G3 cytokine-release syndrome (OSE2101-related) and 2 tumor flares (nivo-related) leading to death were observed in Arm C. Conclusions: Maintenance OSE2101 monotherapy showed a favorable safety profile and encouraging time to strategy failure warranting further evaluation. OSE2101 + nivo was associated with poorer outcomes leading to close Arm C. Following IDMC recommendation, the study is ongoing with the new design (maintenance FOLFIRI vs. FOLFIRI + OSE2101). Clinical trial information: NCT03806309. [Table: see text]
The GERMELATOX-A (Dermatologic Cooperative Oncology Group): Study attitude of German melanoma patients towards toxicity during adjuvant treatment.
Authors: Katharina C. Kähler, Svea Hüning, Dorothée Nashan, Frank Meiss, David A Rafei-Shamsabadi, Hannes Rißmann, Chiara Colapietro, Elisabeth Livingstone, Lara Valeska Maul, Markus V Heppt, Jessica Cecile Hassel, Ralf Gutzmer, Carmen Loquai, Lucie Heinzerling, Michael Max Sachse, Ann-Sophie Bohne, Laura Moysig, Wienke Peters, Judith Rusch, Christine Blome
Journal: Journal of Clinical Oncology (2022)

e21597 Background: Trials of adjuvant treatment with immune checkpoint inhibitors like PD1-antibodies (ICI) or targeted therapy with BRAF/MEK inhibitors (TT) in high-risk melanoma patients demonstrate a significant improvement in recurrence-free survival (RFS) with a very similar relative risk reduction. Both treatment modalities are characterized by specific side effects. Therefore the decision for or against a treatment modality is very often driven by the risk for toxicity. This study addressed for the first time the attitudes and preferences of German and Swiss patients and physicians for adjuvant treatment with ICI and TT. Methods: In this multicenter study („GERMELATOX-A“) patients with low-risk melanoma (pT1a, AJCC stage I, familiar with cancer diagnosis but no adjuvant treatment planned), and dermatooncologists from 11 German and 1 Swiss skin cancer centers were asked to fill out a questionnaire. Here, side effect scenarios typical for each ICI and TT with mild-to-moderate or severe toxicity and also melanoma recurrence leading to cancer death were described. We asked patients and physicians about the reduction in melanoma relapse (relapse-free survival, RFS) and the survival increase (overall survival, OS) at 5 yrs they would expect to tolerate defined side-effects. Results: Data were obtained from 136/107 patients/physicians, respectively (median age: 59 yrs/32 yrs, 56.2%/67.6% female).Overall, by visual analog scale, patients valued a melanoma relapse worse than all scenarios of side-effects during adjuvant treatment with ICI or TT. In general patients required higher risk reductions for DFS and OS for both ICI and TT and their drug related side effects compared to physicians to accept this treatment. In case of severe side effects, patients needed a 20% higher reduction of relapse rate at 5 yrs for ICI compared to TT (71.4%/50.0%). Physicians required identical relapse reduction rates for ICI and TT in case of severe side effects (42.9%). Conclusions: This study demonstrated a pronounced variation of German and Swiss patient preferences on adjuvant treatment related to drug class specific side effects and outcomes and a clear difference between patients' and physicians' attitudes. This difference might influence decision making for adjuvant treatment options and should therefore also be investigated in further trials for current adjuvant treatment modalities. As adjuvant melanoma treatment with ICI and TT will possibly be implemented in earlier stages soon, precise knowledge of the patient perspective can be helpful for the process of decision making.
Long term implications of covid-19 in pregnancy
Authors: Allyah Abbas-Hanif, Neena Modi, Azeem Majeed
Journal: BMJ (2022)

Complications in pregnancy, including maternal and perinatal deaths, increased with each wave of the covid-19 pandemic.By contrast, serious illness fell in other high risk groups because of vaccines and approved treatments. 1 More than a year after the UK's Joint Committee on Vaccination and Immunisation (JVCI) opened up covid-19 vaccination to pregnant women, 40% of women giving birth have still not received a first dose. 2This is despite a positive benefit-risk profile, endorsement in guidelines, and public health campaigns.Worryingly, 69.5% of black women giving birth have not received any covid-19 vaccine.
DIPG-34. Life and End-of-Life after Diffuse Intrinsic Pontine Glioma diagnosis
Authors: Idoya Serrano Pejenaute, Ricardo López-Almaráz, Aizpea Echebarria, Rosa Adán, Jimena De Pedro, Paula Gonzalez, Jesús Sanchez, Julio López-Bayón, Itziar Astigarraga, Miguel García-Ariza
Journal: Neuro-Oncology (2022)

Abstract INTRODUCTION AND OBJECTIVES: Despite advances in pediatric oncology, Diffuse Intrinsic Pontine Glioma’s (DIPG) life expectancy remains &amp;lt;10% at 2 years, and the mean survival time is 8-10 months from diagnosis. Its location associates multiple symptoms of complex management that condition their quality of life. The aim is to review our experience in the clinical course of the disease and the involvement of palliative care (PC). METHODS: Single-centre retrospective study of patients &amp;lt;18 years diagnosed with DIPG between 2011-2022. A review of the electronic medical record was carried out, recording demographic data, oncological treatments, PC and advance care planning (ACP). RESULTS: We registered 14 patients (2 alive). Median age at diagnosis was 6.4 years (range 3.5-11.9). Median survival from diagnosis was 9.6 months (range 0.5-18) and 3.8 months from progression (range 0.1-12). At diagnosis, 92% received oncological treatment (radiotherapy 75%, chemotherapy 41%, oncolytic viruses 21%, partial resection 8%). After progression, 4 patients received metronomic chemotherapy or re-irradiation and in the last month of life 2 received chemotherapy. In the last 3 months of life, 64% were admitted at least once for progression or end-of-life. In the last month, all received oral dexamethasone. Follow-up by PC team was provided in 64%, with first contact in the last month of life in 36%. ACP was recorded in 4 patients, all of them followed up for PC. Death occurred at home in 33%, hospital in 58%. Palliative sedation was used in 5 patients. CONCLUSIONS: Despite the known prognosis of DIPG, some patients continue receiving oncological treatment after progression and in the last month of life. Contact with PC teams occurred mainly at advanced disease stage. Median survival of children with DIPG is below one year, with multiple symptoms in the progression phase. Therefore, early follow-up by PC teams is recommended.
EPEN-25. A novel spontaneous model of ZFTA-RELA fusion ependymoma
Authors: Sigourney Bell, Claire King, Katherine Wickham Rahrmann, Amir Jassim, Jessica Taylor, Richard Gilbertson
Journal: Neuro-Oncology (2022)

Abstract Ependymomas driven by the ZFTA-RELA fusion account for &amp;gt;70% of all supratentorial ependymomas. These tumours are now recognised in the WHO classification of CNS tumours and have been associated with a poor prognosis. Seven ZFTA-RELA fusion variants have been described: around two thirds of cases are fusion 1. No spontaneous genetically modified mouse models (GEMMS) have been described and current models require invasive intracranial injection (of transduced cells or RCAS-TVA system). Here we describe the first spontaneous GEMM of ZFTA-RELA fusion-driven ependymoma. Nestin-Flx-STOP-Flx-ZFTA-RELA (Fusion 1) or E1alpha-Flx-STOP-Flx-ZFTA-RELA open reading frames were targeted together with luciferase to the Rosa-26 locus. Breeding these mice with Nestin-CreERT2 or Blbp-Cre lines that drive recombination in neural progenitor cells resulted in forebrain tumours that could be tracked with bioluminescence imaging from P20. Tumours displayed NF-kB and L1CAM expression and ZFTA-RELA protein was detected using a novel in-house antibody. Tumours display expression of a known ZFTA-RELA fusion ependymoma transcriptomic signature. ZFTA-RELA tumours can be grown as neurospheres and passaged as allografts in nude mice. We provide the first spontaneous GEMM of this important group of ependymomas. We are now characterising these tumours histologically and transcriptomically relative to the human disease and using these to understand the lineage origins of ependymoma and plan use of conventional and novel treatments.
Neoadjuvant chemotherapy is associated with improved outcomes in patients with stage 1A and 1B pancreatic cancer undergoing surgery: An NCDB study.
Authors: Noah Rozich, Maharaj Singh, Isaac Kriley, James L. Weese, Aaron Chevinsky FACS, Wesley Allan Papenfuss, Geoffrey Bellini
Journal: Journal of Clinical Oncology (2022)

4157 Background: The use of neoadjuvant chemotherapy (NAC) for pancreatic ductal adenocarcinoma (PDAC) has shown clear advantages in locally advanced and borderline resectable disease. The benefit in upfront resectable PDAC is debated. Moreover, in early clinical stages IA/IB, potential benefits including improved R0 resection rate, decreased tumor upstaging, and survival, are not clear. We hypothesize that NAC will be associated with improved outcomes and survival compared to adjuvant therapy in patients with clinical stage IA/IB PDAC. Methods: The National Cancer Database (NCDB) PUFs (2004-2017) were used to perform a retrospective review of patients with clinical stage IA or IB PDAC undergoing surgery. Treatment groups were selected based on timing of chemotherapy. Patients receiving chemotherapy or surgery alone were excluded. Results: We identified 6,613 patients with clinical stage IA or IB PDAC who underwent surgery. The neoadjuvant therapy group (NAT) included 1,533 patients who received neoadjuvant or perioperative chemotherapy, and the adjuvant therapy group (AT) contained 5080 patients who received chemotherapy after surgery. Patients in the NAT had higher rates of T1 and T2 disease and lower rates of T3 pathology compared to the AT (pT1: 18.7% vs 7.8%; pT2: 20.1 vs 18.6%; pT3: 59.3% vs 72.1%, p&lt;0.0001). Additionally, the NAT had significantly higher rates of N0 disease and less N1 pathology (pN0: 54.6% vs 37.5%; pN1: 45.4% vs 62.5%, p&lt;0.0001). The R0 resection rate was higher in the NAT (83.2% vs 62.3%, p=0.0197) and there was less lymphovascular invasion (LVI) compared to the AT (34.8% vs 48.1%, p&lt;0.0001). Using Kaplan Meier estimates, the NAT was associated with improved overall survival (OS) compared to the AT (median OS: 33.4 vs 27.5 months, p&lt;0.0001). On multivariable analysis, R0 resection (HR=0.715, CI: 0.619-0.825, p&lt;0.0001), LVI (HR=1.126, 95% CI: 1.038-1.222, p=0.0043) but not receipt of NAC (HR=0.94, 95% CI: 0.852-1.038, p=0.2229) were independent risk factors for OS. Conclusions: NAC is beneficial in patients with stage IA/IB PDAC undergoing surgical resection as it is associated with improved oncologic outcomes including increased R0 resection rate, decreased tumor upstaging, lymph node metastasis, and LVI. Furthermore, patients receiving NAC were found to have improved survival over those getting adjuvant therapy. Based on these results, we recommend all patients diagnosed with PDAC be considered for NAC prior to surgery. [Table: see text]
Real-world assessment of clinical outcomes in NSCLC patients with MET exon 14 skipping mutation and brain metastases (BM) treated with capmatinib.
Authors: Paul K. Paik, Ravi K. Goyal, Beilei Cai, Mark Price, Keith Davis, Valerie Derrien Ansquer, Nydia Caro, Teddy Rassem Saliba
Journal: Journal of Clinical Oncology (2022)

e21171 Background: Capmatinib, a highly selective and potent MET inhibitor, was approved for patients (pts) with advanced MET exon 14 NSCLC in the US in 2020 based on the GEOMETRY mono-1 trial data. Subgroup analyses from that study showed intracranial (IC) efficacy in pts with BM. However, there were no data on the effectiveness of capmatinib in pts with BM in the real-world setting; IC effectiveness is particularly challenging to study as many pts are also treated with radiation therapy (RT) to the brain. The current study examined real-world clinical outcomes of pts with NSCLC with MET exon 14 skipping mutation and BM who were treated with capmatinib, including those who were RT-naïve. Methods: A retrospective medical record review was performed by panel-based oncologists recruited nationwide in the US. Eligible pts were aged ≥ 18 years, had confirmed BM diagnosis and MET exon 14 skipping mutated NSCLC, started capmatinib therapy in any line following BM diagnosis (with ≥ 1 IC lesion ≥ 10 mm), and had a follow up of ≥ 6 months after starting capmatinib (except death). Modified (pseudo) RECIST and RANO-BM criteria were used for response assessments. Key outcomes were IC and systemic real-world best overall response rate (rwORR), disease control rate (rwDCR), progression-free survival (rwPFS), and time-to-treatment discontinuation (TTD) assessed separately for first-line (1L) capmatinib and immunotherapy (IO)-containing regimens alone or in combination with chemotherapy (CT). The analyses are descriptive in nature. Outcomes were also analyzed in RT-naïve pts (no prior/concurrent BM RT). Results: A total of 68 eligible pt charts were abstracted (median age at BM diagnosis, 64.3 years; 60.3% male; 72.1% treated in academic setting; 83.8% de novo metastatic). For the 1L therapy after BM diagnosis, 80.9% (n = 55) received capmatinib, 16.2% (n = 11) received IO-containing regimens, and 2.9% received CT alone; 29 pts were RT-naive. The IC rwORR in RT-naïve pts was 85.0% for capmatinib 1L and 11.1% for IO 1L (Table). In the overall cohort, the IC rwORR was 87.3% (rwDCR 96.4%) for capmatinib 1L and 27.3% (rwDCR 45.5%) for IO 1L. Median systemic rwPFS was 14.1 months for capmatinib 1L and 5.1 months for IO 1L. The 1-year systemic rwPFS rate was 70.8% for capmatinib 1L and 18.2% for IO 1L. TTD was 13.2 months for capmatinib 1L and 5.1 months IO 1L. Conclusions: This study shows a substantial systemic and IC effectiveness associated with capmatinib 1L use in pts with NSCLC with MET exon 14 and BM in the real-world setting. These findings remain true in RT-naïve pts.[Table: see text]
Apparent Treatment-Resistant Hypertension Across the Spectrum of Heart Failure Phenotypes in the Swedish HF Registry
Authors: Alice M. Jackson, Lina Benson, Gianluigi Savarese, Camilla Hage, Pardeep S. Jhund, Mark C. Petrie, Ulf Dahlström, John J.V. McMurray, Lars H. Lund
Journal: JACC Heart Failure (2022)
Prostatic artery embolization compared to trans-urethral resection of the prostate and prostatic urethral lift: A real-world population-based study
Authors: B.L. Raizenne, X. Zheng, K. Oumedjbeur, J. Mao, K. Zorn, D. Elterman, N. Bhojani, A. Sedrakyan, B. Chughtai
Journal: European Urology (2022)
Minimal residual disease comparison between Ig/TCR PCR versus NGS assays in children with Philadelphia chromosome-positive acute lymphoblastic leukemia: A report from the COG AALL1631 study.
Authors: Thai Hoa Tran, Shalini Reshmi, Ilan Richard Kirsch, John A. Kairalla, Sarah K Tasian, Kirk R. Schultz, Elizabeth A. Raetz, Mary Shago, Andrew J. Carroll, Meenakshi Devidas, Stephen Hunger, Mignon L. Loh, Lewis B. Silverman
Journal: Journal of Clinical Oncology (2022)

10023 Background: Minimal residual disease (MRD) assessment by immunoglobulin/T-cell receptor (Ig/TCR) polymerase chain reaction (PCR) is currently being used in the international pediatric Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph + ALL) trial EsPhALL2017/AALL1631 for risk stratification. MRD concordance has previously been demonstrated between Ig/TCR PCR and flow cytometry in Ph + ALL. We sought to assess concordance of MRD assessment between conventional Ig/TCR PCR and next-generation sequencing (NGS) assays. Methods: MRD was assessed in all pts on AALL1631 by Ig/TCR PCR at end-induction IB; those with MRD &lt;5x10 -4 were classified as standard-risk (SR) and randomized to treatment with imatinib and one of two chemotherapy regimens without hematopoietic stem cell transplant (HSCT), whereas pts with end-induction 1B MRD ≥ 5x10 -4 were considered high-risk (HR) and assigned to HSCT after consolidation chemotherapy. Residual diagnostic and end-induction IB samples from consenting pts were assessed for NGS MRD by the clonoSEQ assay (Adaptive Biotechnologies) in blinded fashion and subsequently compared to Ig/TCR MRD to determine concordance as related to MRD-based HSCT recommendations ( ie, MRD ≥ 5x10 -4 consistent with HR group assignment). MRD values were calculated using the kappa statistic for agreement above chance. Results: Sixty-seven pts had matched samples available for MRD assessment at end-induction 1B by both Ig/TCR PCR and NGS (Table). NGS MRD was evaluable for all 67 pts and stratified as 62 SR (&lt;5x10 -4 ) and 5 HR (≥5x10 -4 ). In contrast, Ig/TCR PCR results were inevaluable for 3 pts (unsatisfactory sample quality) and indeterminate (positive, but not quantifiable) in 4 pts. Of the remaining 60 pts, 55 met SR and 5 HR criteria using Ig/TCR PCR. There was only 1 discordant case between the two methods for MRD-based HSCT recommendation among these 60 pts with a kappa statistic for agreement above chance of 0.88. Conclusions: NGS and Ig/TCR PCR assays were highly concordant in MRD assessment for risk stratification at a threshold of 5x10 -4 in pediatric pts with Ph + ALL enrolled on AALL1631. Of note, the NGS assay yielded MRD results amenable for risk stratification in 100% pts compared to 89.6% for the Ig/TCR PCR methodology. These data support the use of NGS MRD testing for risk stratification in pediatric Ph + ALL.[Table: see text]